Science of Synthesis

Janssen, L. J. N.; Blanco-Ania, D., Science of Synthesis: Click Chemistry, (2021) 1, 402.

There has been an exponential growth in bioorthogonal click chemistry since the introduction of the concept in 2004.[‌3‌] Both strain-promoted azide–alkyne cycloadditions (SPAAC) and strain-promoted alkyne–nitrone cycloadditions (SPANC) provide broad applications in life sciences, such as the visualization of biomolecules, radiolabeling, protein modification, tumor targeting, drug delivery, and cell engineering. The reason for the growth in popularity of these methods can be attributed to the fast kinetics and bioorthogonality of these reactions. Although the kinetics of copper-catalyzed click reactions outcompete these processes, the bioorthogonal properties of SPAAC and SPANC reactions have a greater impact on the development of biomedical applications. One of these properties, namely, nontoxicity toward cells, is an enormous advantage over the cytotoxic catalyst that is required for CuAAC. Another superior property is the inertness of SPAAC and SPANC in biological environments, meaning that the reactions do not interfere with natural processes.

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